Which drug is a substrate of N-acetyltransferase 2?

Which drug is a substrate of N-acetyltransferase 2?

• A. Acetaminophen
• B. Isoniazid
• C. Warfarin
• D. Methimazole

Answer: (B)

N-acetyltransferase 2 carries out acetylation in the liver for a subset of drugs, and people’s NAT2 activity can vary due to genetics, creating fast or slow acetylators. Isoniazid is a classic NAT2 substrate; it is acetylated by NAT2 to acetylisoniazid, and slow acetylators can have higher drug exposure and increased risk of toxicity. The other drugs listed are primarily processed by different pathways: acetaminophen is mainly handled by glucuronidation and sulfation, warfarin is mainly metabolized by cytochrome P450 enzymes (especially CYP2C9), and methimazole is cleared by other hepatic routes not chiefly involving NAT2. So, the drug that is a substrate of NAT2 is isoniazid.

N-acetyltransferase 2 carries out acetylation in the liver for a subset of drugs, and people’s NAT2 activity can vary due to genetics, creating fast or slow acetylators. Isoniazid is a classic NAT2 substrate; it is acetylated by NAT2 to acetylisoniazid, and slow acetylators can have higher drug exposure and increased risk of toxicity. The other drugs listed are primarily processed by different pathways: acetaminophen is mainly handled by glucuronidation and sulfation, warfarin is mainly metabolized by cytochrome P450 enzymes (especially CYP2C9), and methimazole is cleared by other hepatic routes not chiefly involving NAT2. So, the drug that is a substrate of NAT2 is isoniazid.